The purpose of the research outlined in this proposal is to combine cell biological, electrophysiological, and behavioral techniques to probe the morphological basis of two fundamental issues central to the study of behavior: 1) the relation between nonassociative and associative learning and 2) the relation between the mechanisms of short- and long-term memory. Toward this end a model system will be used, the gill- and siphon-withdrawal reflex of the marine mollusc Aplysia californica which undergoes a form of associative learning -- classical conditioning as well as two elementary types of nonassociative learning -- habituation and sensitization -- both of which demonstrate a short- and long-term memory. Several aspects of the biophysical and biochemical mechanisms of these forms of learning and memory are known and involve changes in function at a common locus -- the synapses of identified sensory neurons. We have recently demonstrated that long-term habituation and sensitization also produce changes in structure at the sensory neuron synapses. We now propose to explore the mechanisms that underlie these morphological alterations as well as to begin an examination of the nature and extent of structural changes at sensory neuron synapses that may accompany classical conditioning and the short-term form of habituation and sensitization. The intracellular labeling and serial reconstruction approaches we have developed and the model system we plan to use provide the required specificity to address these problems directly. Results from these studies should increase our understanding of the role that morphological alterations at the synapse play in the initiation and maintenance of changes in functional efficacy that mediate various forms of learning and memory. In this fashion we hope to gain additional insights into the cellular relationships between both nonassociative and associative processes as well as the family of morphological events that may contribute to the progressive development of memory storage.